The world’s aging population is expected to facilitate a 50% increase in the global incidence of cancer over the next two decades, with the World Health Organisation (WHO) predicting that new cases will increase from 10million in 2000 to 15million in 2020.

FORTUNATELY, over the next ten years, numerous new novel cancer treatments with improved efficacy and side effect profiles are expected to hit the marketplace. However a new report from independent market analyst Datamonitor* (DTM.L) has suggested that despite the undoubted medical benefits of the new treatments, economic constraints may restrict the uptake of the new drugs, especially in already cash-strapped national health systems.

Putting a price on treatment

Datamonitor expects that pharmacoeconomic constraints will exert an increasingly influential role in the uptake of novel molecular- targeted cancer therapies, Datamonitor Oncology analyst Nish Saini says. “Even in the USA, where pricing policies have historically been less restrictive, the fiscal challenges resulting from spiralling healthcare costs and the recent Medicare Modernisation Act may lead to an era of greater price regulation.” “In terms of cancer treatment, this may lead to a widening of the gap between the ‘haves’ and ‘have-nots’ of the medical world, with these new medications likely to be beyond the reach of those in the developing world, for example. However, perhaps like HIV/AIDS treatments, with the help of western governments, we may see a trickle-down effect over time.” The new treatments may also place western governments, in particular, under increasing pressure to loosen the national healthcare purse strings, Saini says. “Many cancer sufferers in first world economies may be unwilling to accept that they cannot have access to the best available treatment because of budget restrictions. They may ask: how do you put a price on people’s health, well being and quality of life?” “On a practical level, this may lead government- controlled bodies to undertake robust pharmacoeconomic analysis to evaluate the clinical benefit realised with targeted therapies such as Iressa, Avastin, Erbitux and Tarceva, against the cost pressures incurred by these innovations. However in situations where these parameters are incongruent, reimbursement will prove challenging.” Where the uptake of novel treatments is constrained by the pharmacoeconomic pressures associated with these new technologies, improved diagnostic and prognostic analyses will facilitate predictive targeting of treatments to patient populations most likely to respond, Saini says.

New approach, better efficacy

Until recently, pharmacotherapeutic approaches to cancer therapy have been relatively unsophisticated, non-selective in nature and indiscriminately target both malignant and non-malignant cells. “For many tumour types, the relatively unpredictable duration of response to standard chemotherapy approaches means that there is a tremendous unmet need for improved treatment strategies in both early and latestage disease.” Historically the approaches to identifying new cancer treatments have been relatively unsophisticated, relying on crude measures of cancer cell growth or inhibition in animals and test tubes, Saini says. “However with the emergence of new technologies and an increased understanding of the molecular basis for cancer evolution, the molecular changes that distinguish malignant cells from normal cells are becoming increasingly apparent.” “This offers a growing range of potential drug targets in the form of altered genes, proteins or corrupted pathways. The increased selectivity offered by these unique targets affords developers the opportunity to cultivate more efficacious and less toxic treatments, the archetypal example being Novartis’s Glivec which garnered sales of $757m in the first half of 2004.” Molecular treatment targets may be tumour-site specific (such as the Bcr-Abl tyrosine kinase targeted by Glivec) or exhibit commonality between tumour-types (for example, EGFR), Saini says. “The latter offers developers the potential of horizontal product expansion and enhanced product revenues, which is increasingly important given the economic constraints that may restrict the uptake of these novel therapies.” Current cytotoxic agents (chemotherapy) are associated with a high level of toxicity, due to their non-selective pharmacology in targeting all rapidly dividing cells, Saini says. “Common toxicities associated with many frequently used drugs include anaemia, nausea, vomiting, diarrhoea, alopecia, infertility and general fatigue. For patients with terminal disease, the maintenance of quality of life is paramount and significant drug toxicities may jeopardise this.” “Overall, Datamonitor believes the angiogenesis and signal transduction inhibitor classes provide the greatest revenue potential.”

Datamonitor plc (DTM.L) is a premium business information company specialising in industry analysis. We help our clients, 5000 of the world’s leading companies, to address complex strategic issues. Through our proprietary databases and wealth of expertise, we provide clients with unbiased expert analysis and indepth forecasts for six industry sectors: Automotive, Consumer Markets, Energy, Financial Services, Healthcare, Technology. Datamonitor maintains its headquarters in London and has regional offices in New York, San Francisco, Sydney, Tokyo, Frankfurt, Shanghai and Hong Kong. See www.datamonitor.com for further details.

I have come to realise that many ‘discussions’ around a sales call come down to ‘beliefs’. And to ‘effect change in one’s beliefs’ relies on logic, reasoning and premise (in essence – argument). Following on from the series of ‘Tell Sell Neurolinguistics’, I have decided to highlight key aspects of reasoning and argument and how this interacts with beliefs of the customer and interestingly, beliefs of the representative.

Over the next few issues of the MATRIX (Pharma-logically Speaking) it may well be worth looking at the arguments and rational to support your product and ask yourself how they fit in with the examples described below. More importantly from the customer’s perspective and pharma-logically speaking, is your product really the best?

INTRODUCTION TO ARGUMENT

The ability to reason is a well-defined skill. Don’t think that just because your company has come up with a ‘prepared reasoning’ for your product that you don’t require reasoning skills. Because from the customer’s perspective, once you have gained access, revealed you are a friendly/nice/trustworthy/reliable individual, your ability to reason will now make or break your sale. I can tell you there are many representatives who have access but who don’t (and never will) have the sales. Not necessarily because the product is no good, but because the representative is unable to convey this in a compelling way. YOUR SALES PITCH Any argument has a conclusion in mind. The conclusion comes from a number of premises that you will use to justify your claim. Look at your sales/detail interaction. What are the premises? Does it provide the right conclusion? More importantly, could it provide a number of conclusions (ie ambiguity)? Don’t just bask in the good calls. Why are some of your customers not following your train of thought? A starting point may be to ask yourself the following question – does my sales pitch rely on a deductive argument or an inductive argument?

THE DEDUCTIVE ARGUMENT (SLaw, 2003)

The deductive argument follows a preset of rules that is all conclusive. Let’s look at this argument.

• Statins have been found to lower coronary events
• Our product is a statin
• THEREFORE our product will lower coronary events

The deductive argument usually has a ‘therefore’ as we are deducing the conclusion from a set of premises. With the above sales pitch, many customers will have no problem following this deductive argument. So let’s push this argument further.

• Statins have been found to reduce death from CHD
• Our product is a statin
• THEREFORE our product will reduce death from CHD

Now we have a more challenging argument. This one requires that the customer deduces that your product will save lives (well we all want to save lives don’t we!) But this time you may find a mixed response from customers. Why? The premise looks sound. Why would a customer agree with the 1st argument but not the 2nd one? For this we need to evaluate what makes a good deductive argument. There are 2 essential ingredients to a sound deductive argument. Firstly, the premises you are putting forward must be true. Hence a customer may want ‘proof’ or ‘evidence’ for your premises. Many companies fail at this 1st step and hence the representative is left flailing in the cold (ever feel your drug is better than the detail aid that has been given to you?) The second ingredient entails that the premises must also logically entail the conclusion (ie validity). If we turn the conclusion around and say ‘our statin will not reduce death from CHD’ we are denying the conclusion to the point of contradiction. The key to this argument stems on whether ‘all statins’ have been found to reduce death or whether just ‘some statins’ have been found to reduce death. Asserting this premise requires in-depth knowledge of statin trials with correlation of mortality indices and crucial to the premise the exact correlations within the studies which themselves support the premise as well as the deductive argument. (Stop for a moment – reread this last sentence – stop again – and reread it again). Without fluent conversation of these facts, you will find you and your customer are arguing in circles without agreement on your product claims.

THE INDUCTIVE ARGUMENT (SLaw, 2003)

The inductive argument differs from the deductive argument - whilst premises are also provided to support the argument, they do not inherently require your customer to use logic to get a buy-in to your product. See the example below.

The inductive argument does follow a logical stream though it relies more on observation than a logical deduction. We could examine 1000 ...

WHY DID YOU join the industry and become a sales person? Was it to sell through managing your own territory and influencing prescribers, or to simply deliver a list of inflexible key messages with little opportunity to display your initiative? In the past 10 years there has been a huge shift from small, family owned, product linked representatives, to large, matrix managed, faceless entities. A large company 10 years ago had 400 representatives, now you would expect 1000 or more in the UK alone. This begs the question; How can a sales representative drive their business and remain accountable for sales outcomes with large team of people selling the same product to the same customers? This can be a very disheartening prospect for a medical representative who hopes to get noticed and further their career. This isn’t the only option though. Working for smaller to medium sized companies can be very different, and in comparison very personally rewarding. The characteristics of successful people in small and medium companies such as LEO, Merck, Napp, Schering Health Care and Solvay are not dissimilar to those in large companies. Successful people exhibit behaviours such as:

• Desire for success
• Goal orientation
• Taking responsibility
• Enjoy influencing people
• Accountability for action
• Wanting to be the best
• Entrepreneurial spirit

All of these behaviours support, foster, and nurture high levels of accountability, autonomy, and independence which appear to motivate and reward individuals in small to medium sized companies. These characteristics mean that successful people are automatically more suited to working in a smaller company because their high levels of accountability are more easily noticed and therefore rewarded. The differences felt by representatives working in the smaller sector are that they retain individualism, are more easily recognised by customers and can readily measure their success through their own individual sales figures. To further investigate this we asked representatives from small to medium sized companies about their thoughts on accountability and autonomy.

Keith Burston worked for Pharmaceutical giant, now GSK (Glaxo Smith Kline) for 22 years and left to join small to medium size company, Napp Pharma. He had this to tell us about accountability and autonomy. “Napp is interested in delivering the bottom line and providing you with the support and flexibility to do that. You can decide which GP’s to see and who is going to drive your business and that provides the scope to go after the real business. It feels good to have the ability to run your territories like your own franchise and ultimately if the business doesn’t come in, you’re accountable, and there is no one to blame. You have to conscientious, and at the end of the day… autonomy and accountability come with responsibility. It has been amazing to me the change in me and my business. This ability to run my own business has re-energised me and the change has been the best decision for me and my career.” Foster and supporting high levels of independence and autonomy can impact on all areas of a Medical Representatives career, including their own development and career progression. Career development pathways have been described as highly focused, well-defined, and fast moving in a small and medium size companies. Career progression also appears more rapid for those successful people demonstrating a desire for success and outstanding sale performance.

David Southern, Marketing Manager Napp Pharmaceuticals, began as representative in the field for 18 months, then spent six months as a Health Service Manager, and presently works in head office as a marketing manager. He told us: “Everyone knows everyone in a small company from marketing to production. This can be a real advantage when looking at career opportunities and development. Progression can be very fast and seems to be moving and developing continuously. My career has been driven by the interests I have, not a set path, and I am encouraged to experience opportunities along the way. I have the opportunity in a small company to experience and am involved in every area of the business, internal and external. It provides me with a through understanding of the whole business, not just marketing.”

David Southern carries on explain how autonomy can impact and change the business. “In smaller companies there is a tight relationship to the business or emotional attachment to the business, you are not just a number, you are a person and there is no anonymity whatsoever. However, it provides a great challenge and much broader working experience in all areas of the business.”

Steve Smith Primary Care Account Manager at Schering Health Care had this to say about his level of autonomy, “We are masters of our own trade, following our ideas and running a territory as our own business. Our thought processes become clear as we plan meticulously, and we are allowed to take time to concentrate and fine tune the details leading to high success. We have the luxury to cherry pick who we want to work with to drive our business. This is a small organisation so there is no room for error. We cannot afford mistakes.” These behaviours that characterise successful people are the same, regardless of the size of company, but the question remains . . . will they be recognised and highlighted in a large matrix managed entity? Steve joined the industry 6 years ago from 10 years in grocery retailing and finds he gets more recognition for his work. “I am lucky in that I can speak to the directors about a project and feel confident approaching them. You can expect a quick turn around on approval for projects. It is a great feeling that within a small organisation, you can speak to the decision makers just by picking up the phone and speaking to them directly. It feels good to have the CEO give you a pat on the back and tell you to your face that was a job well done.”

Keith Burston, Napp Pharmaceutical, comments having worked for GSK twenty- plus years and now Napp for two and half. “You have the choice, you can be a big fish in a small pond or small fish in a big pond. I know where I am the happiest and feel I get the recognition for hard work and sales success.” It would seem then, that autonomy and accountability are very much alive and kicking in small to medium sized companies, and seem to be the main contributor to the overall job satisfaction for the representatives we spoke to. The only variable that remains to be investigated is company culture. How does company culture motivate people? How do the representatives feel within that company culture? Does the company culture truly encourage and reward success, in conjunction with a healthy work/life balance?

Culture will be the topic in next month’s final article in the series. We will to looking in depth, at company culture, and the differences in culture amongst 5 small to medium sized companies.

While the issue of clinical trial transparency has long been an area of controversy, the matter has certainly hit the headlines in recent months. As a result, the pharmaceutical industry stands firmly in the public gaze and effectively stands accused of promoting a bias to the publication of positive clinical data and the suppression of negative data - to the alleged detriment of consumers.

Why has this issue come to the fore now? The trigger was pulled in June 2004, when New York Attorney General Eliot Spitzer accused GlaxoSmithKline of suppressing information regarding the effectiveness and safety of Paroxetine in adolescents. Apparently spurred into action by this potentially damaging event, GSK announced it was creating the first clinical trial database to publicly disseminate information on GSK sponsored clinical trials. Other companies (including Merck and Eli Lilly) were quick to follow suit. Then in September 2004, in a co-ordinated industry response, PhRMA (The Pharmaceutical Research and Manufacturers of America) announced the launch of a voluntary clinical trials database for the publication of the results of clinical studies conducted with marketed drugs. This database is intended to involve the broad participation of PhRMA membership, although as a voluntary initiative, this is not guaranteed. Coincident with the PhRMA initiative, the International Committee of Medical Journal Editors (ICMJE) issued a statement indicating that, if a clinical study is to be considered for future publication in its member journals, then that clinical study must be listed in a public registry (at or before the onset of patient enrolment). The statement sets out to prevent selective reporting and publication bias in favour of positive results. Enter the politicians. Representative Henry Waxman and Senator Ted Kennedy have since indicated that they intend to introduce legislation mandating publication of all clinical trial results on a government website. The issue of clinical trial transparency has thus become highly charged. What does all this mean? Clearly the pharmaceutical industry is under pressure and the PhRMA initiative could be perceived as a timely response. Widespread adoption can only help to improve public image and restore trust in the industry. Importantly, rapid and successful implementation of this initiative could allow the industry to retain some control on its release of clinical data - hence the implementation date of October 1, 2004. Conversely, anything that is perceived as a delaying tactic is only likely to fuel the debate further. But even with the PhRMA initiative underway, the debate is likely to continue as the proposed database has already attracted criticism given

• The voluntary nature of industry participation
• The summary nature of the data to be made available (as opposed to full access to unpublished trials)
• The concern with self regulation given the direct involvement and potential influence of the industry in the database

The resultant conclusion is that stakeholders beyond the industry will continue to press for complete transparency. What is deemed acceptable disclosure could be a key ‘battleground’. However, it could also be argued that the PhRMA initiative is too little, too late. Based on the Paroxetine/Spitzer case, it has already been proposed that antidepressants carry a black box warning on a potential increase in suicidal ideation in children. This is a potentially significant development. It will not be difficult for some to draw the conclusion that appropriate use of antidepressants has been negatively influenced by the way the disclosure of clinical trial results has been managed. This may play into the hands of those who favour a mandatory program. Similarly, the ICMJE initiative poses a challenge for the industry. Assuming that the industry will want to continue to publish major clinical studies in prestigious peer reviewed journals, then compliance appears inevitable. That ‘interaction’ with other health stakeholders (particularly the medical profession) is an important step in influencing medical practice. However, the inevitable concern is that any move that increases transparency could have negative consequences for the pharmaceutical industry and could lead to

• Violation of IP rights with competitors gaining easier, deeper, and earlier insight on competitor activity - raising the issue of confidentiality and competitive advantage
• Fewer new products entering development if increasing transparency leads to erosion of the value of differentiating factors
• Fewer studies in potentially risky populations (potentially narrowing treatment populations)
• More rigor in the design and conduct of clinical studies (thus increasing the cost of R&D) as the industry seeks to ameliorate risk

From an overall industry perspective, the ability to shoulder the financial risk of potentially negative clinical study results rests with big pharma. Biotechs/small enterprises are increasingly unlikely to be able to bear the risks and additional cost of R&D. This could have important consequences for industry structure. Of course, moves to increase clinical trial transparency will be welcomed by other stakeholders - particularly consumers and payers given the strengthening of the body of clinical evidence which should promote better, more robust, decision making. The practice of evidence based medicine is clearly inhibited if only part of the evidence is in view. Conclusions The clear risk to the industry is that publication of negative/equivocal trial results could undermine the commercial status of a given product. Equally, failure to enter a study in registry/ database initiatives may tarnish a company and its product(s) to the extent that a given product may not be fully adopted into medical practice. Arguably, registering a clinical trial could result in some loss of competitive edge and potential loss of commercial advantage. That may become an inevitable consequence of the pressures emerging from other stakeholders. The key for the pharmaceutical industry may rest in active participation and the exertion of some influence on the final shape of these database/registry initiatives. This in turn could reduce negative impact (for the industry) while improving the image of the industry in the eyes of consumers. However, the jury is still out on how the clinical trial transparency issue will resolve. One thing is certain, as we enter the final stages of the US Presidential campaign, the issue is not going to go away - the debate will continue.